Scientists Sequence Genomes of Malarial Parasite and Mosquito

Malaria continues to plague the world's population, particularly inhabitants of sub-Saharan Africa, where it kills at least one person every 30 seconds. Efforts to eradicate the disease in the 1950s and 1960s met with failure, and current control measures such as antimalarial drugs are swiftly losing their potency. Now researchers have sequenced the genetic codes of the most deadly malarial parasite and a mosquito that carries it. Scientists hope the findings, published this week in the journals Science and Nature, will aid in the development of novel approaches to combating the disease.

Writing in Nature, a team of more than 150 scientists describes the genome of Plasmodium falciparum, a parasite that causes malaria. The analysis, which took six years to complete, identified 14 chromosomes containing almost 5,300 genes, including nearly 200 that produce proteins to help P. falciparum evade the body's defense mechanisms. A better understanding of their functions may point to potential new targets for antimalarial drugs.

Because transmission of malaria requires a mosquito vector, controlling or killing the insects is another route to disease control. To that end, the work published in Science could help. A consortium of researchers led by Celera Genomics has sequenced the DNA of Anopheles gambiae, the primary species of mosquito that transmits malaria to humans. According to the report, the genome is 278 million bases long and contains almost 14,000 genes. The scientists have started the daunting task of identifying their functions. In particular, they investigated which genes were turned on or off when female mosquitoes feed on blood. "Those are the pathways that are likely to be useful in finding points of intervention for developing new insecticides or transmission-blocking vaccines," says lead study author Robert A. Holt of Celera. "I think the most important thing the genome will facilitate in the immediate future is understanding the molecular basis of resistance to insecticides, and finding new insecticide targets."

Additional research published in both journals has shed further light on both P. falciparum and mosquito genetics. Laurence J. Zwiebel of Vanderbilt University and his colleagues pinpointed 276 genes that are critical to A. gambiae's sensory systems, which it uses to identify its human prey. If they can identify those that the mosquito uses to smell humans, Zwiebel says, it could be possible to create new repellants against the pests. Kenneth Vernick of New York University School of Medicine and his colleagues have discovered genes in natural populations of A. gambiae that confer resistance to the malarial parasite, allowing the insect to act as a vector while not succumbing to the disease.

Researchers with the World Health Organization's Special Program for Research and Training in Tropical Diseases in Switzerland describe the new findings, particularly the genome sequences, as a breakthrough for public health and "a major contribution to efforts to combat malaria and other mosquito-borne diseases." Despite these encouraging words, however, actually using the information to save lives will most likely require more money than the $200 million currently available each year for malaria research, scientists say. The required funds will near several billion dollars a year for a generation or so, writes Jeffery D. Sachs of the Earth Institute of Columbia University in a commentary in Science. Although that amount may seem daunting, he concludes, it "will be a very small price to pay for millions of lives saved per year and for hundreds of millions of people to be given the change to escape from the vicious cycle of poverty and disease."

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